The present invention relates to magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI), and in particular to operating magnetic resonance equipment to enhance accuracy of spectral properties by substantially eliminating (termed “crushing” herein) the responses from unwanted coherence order pathways before measuring the nuclear magnetic resonance (NMR) signal. In the following, the base magnetic field or static magnetic field may represent the combination of the external magnetic field and the macroscopic effects of the tissue susceptibility.
Nuclear magnetic resonance studies magnetic nuclei by aligning them with an applied constant magnetic field (B0) in direction z and perturbing this alignment using an alternating magnetic field (B1) at radio frequencies (called RF pulses), orthogonal to z. The resulting response to the perturbing magnetic field is the phenomenon that is exploited in magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). Spatial distributions of the measured spectroscopy are determined by adding to B0, the strength in the z direction, a spatial gradient of the z direction magnetic field along each of three orthogonal coordinate dimensions (e.g., x, y and z) designated Gx, Gy, Gz, respectively.
The elementary particles, neutrons and protons, composing an atomic nucleus, have the intrinsic quantum mechanical property of spin. The overall spin of the nucleus is determined by the spin quantum number I. If the number of both the protons and neutrons in a given isotope are even, then I=0. In other cases, however, the overall spin is non-zero. A non-zero spin is associated with a non-zero magnetic moment, μ, as given by Equation 1a.μ=γI  (1a)where the proportionality constant, γ, is the gyromagnetic ratio. It is this magnetic moment that is exploited in NMR. Without an external magnetic field, the spins are randomly oriented. In the presence of a magnetic field, nuclei that have a spin of one-half, like Hydrogen nuclei (1H), have two possible spin states (aligned with the applied field, referred to as spin up, and anti-aligned, referred to as spin down) with respect to the external magnetic filed. The interaction between the nuclear magnetic moment and the external magnetic field means the two states do not have the same energy. The energy difference between the two states is given by Equation 1b.ΔE=ℏγB0  (1b)where ℏ is Plank's reduced constant. While most atoms are still oriented randomly, in thermal equilibrium, more than average atoms will be in the lower energy state and fewer than average in the high energy state imparting a net magnetization vector in the direction of the applied external magnetic field.
Resonant absorption will occur when electromagnetic radiation of the correct frequency to match this energy difference is applied. The energy of photons of electromagnetic radiation is given by Equation 2.E=hf  (2)where f is the frequency of the electromagnetic radiation and h=2πℏ. Thus, absorption will occur when the frequency is given by Equation 3.f=γB0/(2π)  (3)The NMR frequency f is shifted by the ‘shielding’ effect of the surrounding electrons. In general, this electronic shielding reduces the magnetic field at the nucleus (which is what determines the NMR frequency). As a result, the energy gap is reduced, and the frequency required to achieve resonance is also reduced. This shift of the NMR frequency due to the chemical environment is called the chemical shift, and it explains why NMR is a direct probe of chemical structure. Gradually the high energy state nuclei lose their excess energy to the lower state nuclei and return to a random distribution at an exponential decay rate called the T1 relaxation time.
Applying a short electromagnetic pulse in the radio frequency range to a set of nuclear spins induces a transition between states of the spins. In terms of the net magnetization vector (which is due to the fact that while many nuclei are randomly arranged, there is some alignment in the spins, i.e., more nuclei have nuclear magnetic moments aligned than anti-aligned with the field), this corresponds to tilting the net magnetization vector away from its equilibrium position (aligned in the z direction along the external magnetic field, B0). The out-of-equilibrium magnetization vector processes about the external magnetic field at the NMR frequency of the spins. This oscillating magnetization induces a current in a nearby pickup coil acting as a radio frequency (RF) receiver, creating an electrical signal oscillating at the NMR frequency.
A portion of this time domain signal (intensity vs. time), after all radio frequency pulses, is known as the free induction decay (FID) and contains the sum of the NMR responses from all the excited spins and all their chemical shielding effects. In order to obtain the frequency-domain NMR spectrum (intensity vs. frequency) for magnetic resonance spectroscopy (MRS) and MRS imaging (MRSI), this time-domain signal is Fourier transformed. After the RF pulse ends, the energy in the emitted FID signal decreases at an exponential rate called the T2 relaxation time. The T2 relaxation time is the time for precessing nuclei to fall out of alignment with each other (i.e., lose coherence) and thus stop producing a signal.
Spectral resolution refers to the ability to distinguish two closely spaced peaks in any spectrum. It is one of the important criteria that define the quality of MRS and MRSI. Low spectral resolution can obscure the information available from molecules of interest, such as metabolites, in a volume of tissue, thus making difficult or impossible the detection and quantification of some or all of those metabolites.
Within the category of data acquisition, the most commonly employed strategy for improving spectral resolution is the automated techniques for improving the homogeneity of the magnetic field B0. Fast and high order shimming techniques have been implemented on modern scanners to make B0 more uniform across a subject being scanned, yet these methods cannot eliminate all variation in local magnetic fields that are caused by the differing magnetic susceptibilities of various interposed tissues within the body. To image at higher magnetic field strengths is another strategy to increase spectral resolution, as well as improve the signal-to-noise ratio (SNR) of the MRS. Theoretically, doubling the field strength should double the differences in chemical shifts and the separations peaks in the metabolic spectrum. Unfortunately, the observed benefit of higher field strengths in improving spectral resolution is much lower than theoretically predicted. For higher fields, such as 7 Tesla (T, 1 T=1 Newton per Ampere per meter) and above, there is substantially sub-linear spectral resolution improvement. Two reasons for this are that scanners with higher field strengths come with greater inhomogeneity of their magnetic fields, and the higher fields shorten the T2 relaxation times of metabolites, both of which increase linewidths of the spectrum. In addition, the upper limit on field strength is constrained by practical and safety considerations. Techniques of fast acquisition of data can reduce the total scan time and thereby reduce the likelihood that the person being imaged moves, and this will indirectly reduce the line broadening caused by subject motion. Other acquisition-based techniques are designed to overcome these problems, as such higher spatial resolution MRSI is designed to address low spatial resolution, whereas 2dimensional (2D) J-resolved MRSI overcomes the limited spectral resolution to improve spectral resolvability through a second spectral dimension. However, both of these techniques usually require long scan times which cannot be afforded in many clinical and research applications.
A further phenomenon known to affect the accuracy of spectral properties deduced from the FID, include excitation of higher coherence orders. In the simple vector picture of NMR, the phase of a radiofrequency pulse determines the axis along which the magnetic field, B1 appears. Its phase is represented as the angle, β between a reference axis (e.g., x) and the vector representing B1. If the reference axis is chosen to be aligned with the field B1, then β=0. When precessing nuclei particles interact with surrounding spin-coupled particles (also called coupled particle for convenience herein), the phase of the excited particle can affect the phase of the coupled particle, which can in turn be converted to a higher-order coherence through the application of a subsequent RF pulse. Coherence order is given by a signed integer value, p. A coherence of order p experiences a phase shift of −pφ, where φ is the phase of the RF pulse. Single quantum coherence has p=±1, double has p=±2 and so on; z-magnetization, “zz” terms and zero-quantum coherence have p=0. Coherence orders with values not equal to 1 or −1 are referred to as multiple quantum coherences and are simultaneous transitions between energy levels of coupled spins. The RF induces the transition between coherence order of a particular group of spins. An excitation pulse rotates the initial coherence order of the population from 0 to a coherence order of +/−1.
Depending on the particular application, it is routine to apply multiple RF pulses, for coherence pathway selection and for spatial localization. The RF pulses are timed to be in phase with the excitation pulse but short compared to T2. Such successive pulses also can change the coherence order from the order of the original pulse. Thus one or more additional pulses are employed to return the coherence order to +/−1. The coherence order sequence resulting from the RF pulse sequence is called the coherence pathway of the pulse sequence.
Each RF pulse also has the potential to produce multiple order coherences due to interactions among spin coupled particles, and for most applications they generate undesired signal characteristics, thus it is desirable to reduce or eliminate these higher coherence orders between RF pulses. It was recognized that such coherence orders could be suppressed (termed “crushed”) in gradient magnetic fields that could be produced by the gradient magnet coils used for spatial distribution, so pulses of gradient magnetic fields, Gx, Gy, Gz, called “crushers” are often employed between RF pulses. After an RF pulse, at the beginning of the gradient pulse, the vectors representing transverse (in x-y plane) magnetization in a voxel are aligned, but after some time each vector has precessed through a different angle because of the variation in resonant frequency. After sufficient time the vectors are disposed in such a way that the net magnetization of the sample (obtained by adding together all the vectors) approaches zero. The gradient pulse is said to have de-phased the magnetization. Gradient pulses are employed to de-phase the coherence pathways other than the target coherence pathway and subsequent RF pulses are used to refocus or re-phase the target coherence pathway.